TISSUE FACTOR-INITIATED THROMBIN GENERATION ACTIVATES THE SIGNALING THROMBIN RECEPTOR ON MALIGNANT-MELANOMA CELLS

The human melanoma cell line M24met expresses tissue factor, the cellu lar initiator of the blood coagulation cascade. Blocking of the coagul ation pathways at the level of tissue factor, factor Xa, or thrombin i nhibits hematogenous M24met metastasis in SCID mice, implicating a rol e for thrombin generation in this process. Dependent on cell surface t issue factor activity, M24met cells generate thrombin in vitro. Thromb in and the thrombin receptor agonist peptide TRP-14 activate a signali ng pathway in M24met cells that involves an increase in intracellular calcium and induces cell proliferation. Immunofluorescence evidences e xpression of the signaling thrombin receptor on these cells. Thus, M24 met melanoma cells express both the initiating cell surface receptor f or the coagulation pathways and the central signaling receptor of the coagulation system, suggesting the in situ generation of proliferative signals which can contribute to the malignant phenotype.